1. Field of Invention
The present invention relates to a fluid handling system, apparatus and method. It is particularly useful for sequential introduction of fluids, including gases, liquid samples and processing liquids such as reagents or diluents, into continuous flow analyzers.
2. Brief Description of the Prior Art
Automated apparatus for the analysis of liquid samples as a flowing stream was disclosed by Skeggs in U.S. Pat. Nos. 2,797,149 and 2,879,141, both assigned to the instant assignee. In this basic apparatus, the liquid samples are sequentially aspirated from storage containers into a conduit, each sample being separated from the next successive sample by a segment of air. Air is introduced into the conduit to segment each individual sample to promote intrasample mixing and between successive samples to prevent intersample contamination. As illustrated by Ferrari in U.S. Pat. No. 2,933,293, also assigned to the instant assignee, a junction in the conduit continually introduces a processing liquid, such as a reagent, into the alternating sequence of air and sample segments. Ferrari et al, U.S. Pat. No. 3,109,713, assigned to the instant assignee, also discloses an analysis apparatus in which processing fluids, such as reagents, are continuously introduced into a stream of alternating air and sample segments, as shown at the juncture of conduits 42 and 44 in FIG. 1.
Smythe et al, U.S. Pat. No. 3,479,141, likewise assigned to the instant assignee, discloses a transport system for automatic analysis apparatus in which a series of aqueous liquid samples are processed as a flowing fluid with substantially no contamination between segments. A fluoropolymer conduit and intersample carrier segments of silicone are used. The silicone encapsulates the aqueous liquid segments. Thus, the intermixing of successive liquid segments is substantially completely eliminated.
Bannister, et al, U.S. Pat. No. 3,759,667 discloses a method and apparatus for aspirating a liquid sample followed by increments of diluent, introduced through a different inlet, in precise volumetric ratio to the sample volume, particularly for use in automated analyzers. The apparatus includes an aspirating probe, having a complex apparatus for introducing diluent through a diluent chamber, which vertically reciprocates from a lower, aspirating position to an upper position in which diluent is introduced through the diluent chamber, and thereafter to an intermediate position in which air is aspirated. The aspiration sequence disclosed is (1) serum; (2) diluent; (3) air; (4) diluent; (5) air; (6) diluent, and presumably (7) air. This column of fluids is passed along a conduit by the vacuum action of a downstream proportional pump, through a vertical mixing stage and into an aliquot splitting section for dispensing. This patent teaches that it is necessary to restrain the acceleration which arises when the probe end moves from aspirating relatively heavy fluid to aspirating air. A controlled pulse of air pressure is introduced to compensate for this acceleration.
A first sensor, such as an optical sensor, detects either the diluent/air or serum/air interface and is positioned on the conduit at a distance from the probe tip such that the precise volume of sample is aspirated to that point. A second sensor is positioned further along the conduit and is separated from the first sensor by a helical mixing coil, such that the volume between it and the probe tip is equal to the desired total volume of sample, air and diluent. Signals from these sensors, operating together with and interdependent upon signals from a timing device, are used to control the movement of the aspirating probe and thereby to control the volumetric ratio between the aspirated serum and the aspirated diluent. This patent does not disclose or suggest any possible use for a series of values operating in coordination with the sensors, let alone their use to establish or create discrete fluid segments. In conventional fluid metering systems such as this, positive displacement (pistons) or peristaltic pumps are used, the travel of a piston or roller thus determining the accuracy of flow rate, and, therefore, aspirated segment volume. Control of the creation of such fluid segments is not separated from the control of fluid stream passage by the pump. Also, the metering precision, as well as the driving force, is controlled by the fluid pumping mechanism.
Young, et al, U.S. Pat. No. 3,929,413 discloses a system for forming and transporting small, discrete measured quantities (slugs) of fluid in a conduit, such as in automated chemical analysis apparatus. These slugs are formed by detecting, with suitable detectors, the leading meniscus of a fluid in the conduit and automatically actuating a single, complex valve which is upstream of, e.g., closer to the aspirator than, the detector(s). Essentially, this valve is a magnetic actuator enclosed in a non-magnetic body and responsive to a pair of magnetic fields produced by electrical coils located respectively on inlet and outlet sides of the valve chamber. These slugs are passed through the conduit by a push and pull combination of vacuum upon the leading meniscus and air pressure upon the trailing meniscus which depends upon operation of the valve to, in effect, open the conduit wall and introduce pressurized air. A vacuum applied proximate the dispensing end draws the fluid into and through a probe until a predetermined volume of fluid has been introduced. The flow-controlled metering valve is then actuated, the valve introduces pressurized air to further provide and control the motive force for the fluid stream, and thus the fluid slug is transported by a combination of vacuum and air pressure as described. The patent teaches that this is to be preferred over peristaltic pumping which is independent of valving or detection of fluid stream passage. Further, the motive force here disclosed is neither continuous nor uniform, as evidenced by the configuration of vacuum control valve 211 in FIG. 3a. In fact, it is taught that flow velocity must be measured because of the variations in flow rate caused by slugs of different materials.
As is further disclosed by Young, et al, one or more metering detectors are spaced along the fluid conduit and respond to the passage of the leading fluid meniscus therethrough to automatically close a flow-control valve and form a slug of known volume. Plural detectors are spaced along the conduit to produce slugs of different volume, only one valve being used even with a plurality of detectors. This flow-control valve intersects the stream of liquid and this presents a major risk of carryover contamination.
Each of the above patents have provided an advance of one sort or another in fluid handling, particularly the introduction of samples to automated analysis systems. This end has been widely recognized as a major consideration in the improvement of continuous-flow systems in particular because of their high throughput. Thus, the combined references provide a significant background literature on the technology of samplers for continuous-flow analysis systems.